Comments

Galanin-(1-11) is a high-affinity agonist at GAL1/GAL2 (pKi 9), and galanin(2-11) is selective for GAL2 and GAL3 compared with GAL1 [14]. [125I]-[Tyr26]galanin binds to all three subtypes with Kd values generally reported to range from 0.05 to 1 nM, depending on the assay conditions used [7,21-23,28]. Porcine galanin-(3-29) does not bind to cloned GAL1, GAL2 or GAL3 receptors, but a receptor that is functionally activated by porcine galanin-(3–29) has been reported in pituitary and gastric smooth muscle cells [9,31]. Additional galanin receptor subtypes are also suggested from studies with chimeric peptides (e.g. M15, M35 and M40), which act as antagonists in functional assays in the cardiovascular system [26], spinal cord [30], locus coeruleus, hippocampus [1] and hypothalamus [2,13], but exhibit agonist activity at some peripheral sites [2,9]. The chimeric peptides M15, M32, M35, M40 and C7 are agonists at GAL1 receptors expressed endogenously in Bowes human melanoma cells [16], and at heterologously expressed recombinant GAL1, GAL2 and GAL3 receptors [7,22-23]. Recent studies have described the synthesis of a series of novel, systemically-active, galanin analogues, with modest preferential binding at the GAL2 receptor. Specific chemical modifications to the galanin backbone increased brain levels of these peptides after i.v. injection and several of these peptides exerted a potent antidepressant-like effect in mouse models of depression [18].